The present invention relates to a bioreactor for performing biological and/or biochemical reactions. More specifically, the present invention relates to a bioreactor adapted for applying to quality assessment, analysis and so on, in systems difficult to attain, a uniform dispersion and mixing, such as those in the production of foods, biological samples and drugs etc.
Hitherto, three basic types of bioreactors have found their practical uses in realizing biological and biochemical reactions, namely, a stationary type, a shaking type and a rotating type. In conventional bioreactors, dynamic analyses of reactions have been attempted in general for diluted reaction systems using a low concentration substrate. However, few attempts have hitherto been successful at analyzing reaction systems with highly concentrated or insoluble substrates.
As a common stationary bioreactor, a fixedly settled reaction vessel, such as an Erlenmeyer flask, is employed in which a stirrer is arranged so as to realize a horizontal rotary movement to cause agitation of the reaction mixture, in order to increase the reaction rate. While this bioreactor permits an economical running of reaction, nevertheless, it cannot operate with a highly viscous substrate due to the shortage of driving torque of the stirrer. In this bioreactor, it is also a disadvantage that substrates with densities different from that of the solvent, i.e. the reaction medium, may tend to float up or sediment down to cause a separation of the reaction mixture.
In shaking type bioreactors, a shaking culture using test tubes as the culture vessel has widely been practised. In this system, the reaction is accelerated by reciprocating a horizontal movement of the culture vessel. This bioreactor can not serve for a highly viscous reaction system and, in addition, may encounter a problem of separation of the reaction mixture for a reaction system with a substrate having a density different from that of the reaction medium.
In rotating type bioreactors, those in which a reaction vessel, such as a test tube, with a plug closure is subjected to, for example, a circular motion by means of, for example, a rotator, to cause agitation of the reaction mixture, have found wide uses in practice. These bioreactors are suitable for reactions to be conducted with mild reaction rates, such as in a cell culture. Also in this type of bioreactors, however, the floating up of the substrate occurs for substrates having lower densities than that of the reaction medium and homogeneity may not be attained. In reaction systems evolving gases, the internal pressure will increase due to the tight plug closure, resulting in, occasionally, a leaking out of the reaction mixture. Since the bioreactors of this type are designed in general in a construction in which the reaction vessel, the mechanical driving arrangement and the control unit therefor are integrally combined, the entire installation should be accomodated in a constant temperature room. The employment of a constant temperature room brings about disadvantages in that a large investment is required and that it is accompanied by the occurrence of unstability of temperature upon openening and closure of the room door, since the thermostat therefor uses atmospheric air, which has a low specific heat, as the heat medium.
For improving such disadvantages of the prior techniques, a bioreactor was proposed (Japanese Patent Application Kokai No. 72957/1991), in which a planetary gear is incorporated within the reaction vessel for effecting milling and mixing of the reaction mixture, while imparting a convectional flow to the reaction mixture by a vertically arranged screw conveyer.
Upon operation of this bioreactor, however, the reaction mixture captured by the gear wheels is forced outside by the force generated upon rotation of the wheels, so that a simultaneous attainment of a uniform agitation and a milling effect is difficult for a reaction system with a high content of insoluble solid. Moreover, the construction of the apparatus is complicated. In addition, the milling action by the gear wheels may eventually cause damage to living microorganism.